In vitro biological evaluation and in silico insights into the antiviral activity of standardized olive leaves extract against SARS-CoV-2.

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 µg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.

DFT and molecular simulation validation of the binding activity of PDEδ inhibitors for repression of oncogenic k-Ras.

The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy. Molecular dynamic simulations (MD) will be used to predict the binding conformations and pharmacophoric features in the active site of PDEδ for the examined structures. The binding free energies determined using the MMPB(GB)SA method will be compared with the observed potency values of the tested compounds. This computational approach aims to enhance understanding of the PDEδ selective mechanism, which could contribute to the development of novel selective inhibitors for K-Ras signaling.

Novel indolinone-tethered benzothiophenes as anti-tubercular agents against MDR/XDR M. tuberculosis: Design, synthesis, biological evaluation and in vivo pharmacokinetic study.

Joining the global effort to eradicate tuberculosis, one of the deadliest infectious killers in the world, we disclose in this paper the design and synthesis of new indolinone-tethered benzothiophene hybrids 6a-i and 7a-i as potential anti-tubercular agents. The MICs were determined in vitro for the synthesized compounds against the sensitive M. tuberculosis strain ATCC 25177. Potent compounds 6b, 6d, 6f, 6h, 7a, 7b, 7d, 7f, 7h and 7i were furtherly assessed versus resistant MDR-TB and XDR-TB. Structure activity relationship investigation of the synthesized compounds was illustrated, accordingly. Superlative potency was unveiled for compound 6h (MIC = 0.48, 1.95 and 7.81 µg/mL for ATCC 25177 sensitive TB strain, resistant MDR-TB and XDR-TB, respectively). Moreover, validated in vivo pharmacokinetic study was performed for the most potent derivative 6h revealing superior pharmacokinetic profile over the reference drug. For further exploration of the anti-tubercular mechanism of action, molecular docking was carried out for the former compound in DprE1 active site as one of the important biological targets of TB. The binding mode and the docking score uncovered exceptional binding when compared to the co-crystallized ligand suggesting that it maybe the underlying target for its outstanding anti-tubercular potency.

Comparative metabolic study of the chloroform fraction of three Cystoseira species based on UPLC/ESI/MS analysis and biological activities.

This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The results revealed the identification of 19, 20 and 11 metabolites in C. myrica, C. trinodis, and C. tamariscifolia, respectively mainly terpenoids, flavonoids, phenolic acids and fatty acids. Also, an in vitro antioxidant study using FRAP and DPPH assays was conducted where the chloroform fraction of C. trinodis displayed the highest antioxidant activity in both assays, which would be attributed to its highest total phenolics and total flavonoids. Besides, the investigation of COX-1, α-glucosidase and α-amylase inhibitory activities were performed. Regarding C. trinodis, it showed the strongest inhibitory activity towards COX-1. Moreover, it showed potent inhibitory activity towards α-glucosidase and α-amylase enzymes. According to the molecular docking studies, the major compounds characterised showed efficient binding to the active sites of the target enzymes.

A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.

The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, ß-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.

Phytochemical profiling and neuroprotective activity of Callistemon subulatus leaves against cyclophosphamide-induced chemobrain.

Cyclophosphamide (CPA) is a chemotherapeutic drug used for various types of cancers. However, patients receiving CPA for long periods suffer cognitive impairment associated with difficulties in learning, decreased concentration, and impaired memory. Chemotherapy-induced cognitive impairment, known as chemobrain, has been attributed to enhanced oxidative stress and inflammatory response. The current study aimed to identify the phytoconstituents of Callistemon subulatus extract (CSE) using HPLC-ESI/MS-MS analysis and evaluate its neuroprotective activity against CPA-induced chemobrain in rats. Fourteen compounds were identified following HPLC analysis including, five phlorglucinols, four flavonol glycosides, a triterpene, and a phenolic acid. Forty rats were divided into five groups treated for ten days as follows; group I (control group), group II received CPA (200 mg/kg, i.p.) on the 7th day, groups III and IV received CSE (200 and 400 mg/kg respectively, orally) for ten days and CPA (200 mg/kg, i.p.) on the 7th day, and group V received only CSE (400 mg/kg, orally) for ten days. The administration of CSE effectively ameliorated the deleterious effects of CPA on spatial and short-term memories, as evidenced by behavioral tests, Y-maze and passive avoidance. Such findings were further confirmed by histological examination. In addition, CSE counteracted the effect of CPA on hippocampal acetylcholinesterase (AChE) activity enhancing the level of acetylcholine. Owing to the CSE antioxidant properties, it hindered the CPA-induced redox imbalance, which is represented by decreased catalase and reduced glutathione levels, as well as enhanced lipid peroxidation. Therefore, CSE may be a promising natural candidate for protection against CPA-induced chemobrain in cancer patients.

Exploring natural compound, Panicutine as leucine-rich repeat kinase 2 inhibitor against Parkinson's disease: a structure-guided approach.

Leucine-rich repeat kinase 2 (LRRK2) is a promising drug target for the therapeutic management of Parkinson's disease (PD) and other neurodegenerative disorders. LRRK2 inhibitors have the potential to modulate neuroinflammation, reduce alpha-synuclein aggregation and improve motor symptoms in PD patients. Although LRRK2 inhibitors are still in the early stages of clinical development, the identification of potent and selective inhibitors through structure-guided approaches provides a promising avenue for the development of effective therapies for PD and other neurodegenerative disorders. In this study, natural compounds from the IMPPAT database were screened using a state-of-the-art computational virtual screening approach to identify potential inhibitors of LRRK2. We carried out a docking screening on a library of natural compounds and identified a few compounds with strong binding affinity, docking score and specificity towards LRRK2 as the top hits. These hits were then subjected to further analysis based on multiple parameters for the Pan-assay interference compounds and their physicochemical and pharmacokinetics evaluation followed by a detailed interaction analysis. After careful evaluation, one natural compound, Panicutine, was identified as a promising candidate for LRRK2 due to its significant affinity and specificity towards the LRRK2 binding pocket. Additionally, it exhibited drug-like properties with blood-brain barrier permeability as determined by ADMET properties. To gain a deeper understanding of the stability and conformational changes of the LRRK2-ligand complex, MD simulations were conducted for 100 nanoseconds under explicit solvent conditions followed by principal component analysis and free energy dynamics. The simulation results demonstrated that the LRRK2-Panicutine complex remained stable throughout the simulation trajectories. Based on these findings, it is concluded that Panicutine has the potential to act as a LRRK2 inhibitor against PD and other neurodegenerative disorders.Communicated by Ramaswamy H. Sarma.

Unveiling Phytoconstituents with Inhibitory Potential Against Tyrosine-Protein Kinase Fyn: A Comprehensive Virtual Screening Approach Targeting Alzheimer's Disease.

BACKGROUND: Tyrosine-protein kinase Fyn (Fyn) is a critical signaling molecule involved in various cellular processes, including neuronal development, synaptic plasticity, and disease pathogenesis. Dysregulation of Fyn kinase has been implicated in various complex diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as different cancer types. Therefore, identifying small molecule inhibitors that can inhibit Fyn activity holds substantial significance in drug discovery. OBJECTIVE: The aim of this study was to identify potential small-molecule inhibitors among bioactive phytoconstituents against tyrosine-protein kinase Fyn. METHODS: Through a comprehensive approach involving molecular docking, drug likeliness filters, and molecular dynamics (MD) simulations, we performed a virtual screening of a natural compounds library. This methodology aimed to pinpoint compounds potentially interacting with Fyn kinase and inhibiting its activity. RESULTS: This study finds two potential natural compounds: Dehydromillettone and Tanshinone B. These compoundsdemonstrated substantial affinity and specific interactions towards the Fyn binding pocket. Their conformations exhibitedcompatibility and stability, indicating the formation of robust protein-ligand complexes. A significant array of non-covalentinteractions supported the structural integrity of these complexes. CONCLUSION: Dehydromillettone and Tanshinone B emerge as promising candidates, poised for further optimization as Fynkinase inhibitors with therapeutic applications. In a broader context, this study demonstrates the potential of computationaldrug discovery, underscoring its utility in identifying compounds with clinical significance. The identified inhibitors holdpromise in addressing a spectrum of cancer and neurodegenerative disorders. However, their efficacy and safety necessitatevalidation through subsequent experimental studies.

2,4-Diaryl-pyrimido[1,2-a]benzimidazole derivatives as novel anticancer agents endowed with potent anti-leukemia activity: Synthesis, biological evaluation and kinase profiling.

Acute myeloid leukemia (AML) stands as one of the most aggressive type of human cancer that can develop rapidly and thus requires immediate management. In the current study, the development of novel derivatives of pyrimido[1,2-a]benzimidazole (5a-p) as potential anti-AML agents is reported. The prepared compounds 5a-p were inspected for their in vitro anti-tumor activity at NCI-DTP and subsequently 5h was selected for full panel five-dose screening to assess its TGI, LC50 and GI50 values. Compound 5h showed effective anti-tumor activity at low micromolar concentration on all tested human cancer cell lines with GI50 range from 0.35 to 9.43 µM with superior sub-micromolar activity towards leukemia. Furthermore, pyrimido[1,2-a]benzimidazoles 5e-l were tested on a panel ofhuman acute leukemia cell lines, namely HL60, MOLM-13, MV4-11, CCRF-CEM and THP-1, where 5e-h reached single-digit micromolar GI50 values for all the tested cell lines. All prepared compounds were first tested for inhibitory action against the leukemia-associated mutant FLT3-ITD, as well as against ABL, CDK2, and GSK3 kinases, in order to identify the kinase target for the herein described pyrimido[1,2-a]benzimidazoles. However, the examined molecules disclosed non-significant activity against these kinases. Thereafter, a kinase profiling on a panel of 338 human kinases was then used to discover the potential target. Interestingly, pyrimido[1,2-a]benzimidazoles 5e and 5h significantly inhibited BMX kinase. Further investigation for the effect on cell cycle of HL60 and MV4-11 cells and caspase 3/7 activity was also performed. In addition, the changes in selected proteins (PARP-1, Mcl-1, pH3-Ser10) associated with cell death and viability were analyzed in HL60 and MV4-11 cells by immunoblotting.

Chemical composition, seasonal variation and antiaging activities of essential oil from Callistemon subulatus leaves growing in Egypt.

Callistemon is an aromatic genus of flowering plants belonging to family Myrtaceae. The essential oils of C. subulatus leaves were collected in four seasons and analyzed using GC/MS. The oils demonstrated monoterpenes as the predominant class. Eucalyptol was the main component in all seasons; summer (66.87%), autumn (58.33%), winter (46.74%) and spring (44.63%), followed by α-pinene; spring (31.41%), winter (28.69%), summer (26.34%) and autumn (24.68%). Winter oil, the highest yield (0.53 mL/100g), was further investigated for its inhibitory activity against enzymes associated with ageing; elastase and acetylcholinesterase. It remarkably inhibited elastase and acetylcholinesterase with IC50 values of 1.05 and 0.20 µg/ml, respectively. A molecular docking study was conducted for the major oil components on the active sites of target enzymes. Eucalyptol revealed the best binding affinity for both enzymes. C. subualtus oil could be used as supplement for management of ageing disorders like skin wrinkles and dementia.

An updated review of fatty acid residue-tethered heterocyclic compounds: synthetic strategies and biological significance.

Heterocyclic compounds have been featured as the key building blocks for the development of biologically active molecules. In addition to being derived from renewable raw materials, fatty acids possess a variety of biological properties. The two bioactive ingredients are being combined by many researchers to produce hybrid molecules that have a number of desirable properties. Biological activities and significance of heterocyclic derivatives of fatty acids have been demonstrated in a new class of heterocyclic compounds called heterocyclic fatty acid hybrid derivatives. The significance of heterocyclic-fatty acid hybrid derivatives has been emphasized in numerous research articles over the past few years. In this review, we emphasize the development of synthetic methods and their biological evaluation for heterocyclic fatty acid derivatives. These reports, combined with the upcoming compilation, are expected to serve as comprehensive foundations and references for synthetic, preparative, and applicable methods in medicinal chemistry.

Insight into the Biological Roles and Mechanisms of Phytochemicals in Different Types of Cancer: Targeting Cancer Therapeutics.

Cancer is a hard-to-treat disease with a high reoccurrence rate that affects health and lives globally. The condition has a high occurrence rate and is the second leading cause of mortality after cardiovascular disorders. Increased research and more profound knowledge of the mechanisms contributing to the disease's onset and progression have led to drug discovery and development. Various drugs are on the market against cancer; however, the drugs face challenges of chemoresistance. The other major problem is the side effects of these drugs. Therefore, using complementary and additional medicines from natural sources is the best strategy to overcome these issues. The naturally occurring phytochemicals are a vast source of novel drugs against various ailments. The modes of action by which phytochemicals show their anti-cancer effects can be the induction of apoptosis, the onset of cell cycle arrest, kinase inhibition, and the blocking of carcinogens. This review aims to describe different phytochemicals, their classification, the role of phytochemicals as anti-cancer agents, the mode of action of phytochemicals, and their role in various types of cancer.

Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: synthesis, biological evaluations and modelling insights.

Multiple inhibitions of CA, COX-2 and 5-LOX enzymes has been recognised as a useful strategy for the development of anti-inflammatory drugs that can avoid the disadvantages of using NSAIDs alone. Here, we report new pyridazine-based sulphonamides (5a-c and 7a-f) as potential multi-target anti-inflammatory candidates. First, the furanone heterocycle in the dual CA/COX-2 inhibitor Polmacoxib was replaced with the pyridazinone one. Then, a hydrophobic tail was appended through benzylation of the 3-hydroxyl group of the pyridazinone scaffold to afford benzyloxy pyridazines 5a-c. Furthermore, the structures were adorned with the polar sulphonate functionality, in pyridazine sulphonates 7a-f, that are expected to be engaged in interactions with the hydrophilic half of the CA binding sites. All of the disclosed pyridazinones were tested for inhibitory activities against 4 hCA isoforms (I, II, IX, and XII), as well as against COX-1/2, and 5-LOX. Furthermore, in vivo anti-inflammatory and analgesic effects of pyridazinones 7a and 7b were examined.

Metabolomic profile, anti-trypanosomal potential and molecular docking studies of Thunbergia grandifolia.

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 µg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves.

WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-ß/ß-catenin/α-SMA pathway.

Hepatocellular carcinoma is considered one of the most lethal cancers, which is characterised by increasing prevalence associated with high level of invasion and metastasis. The novel synthetic pyrazolo[3,4-b]pyridine compound, WRH-2412, was reported to exhibit in vitro antitumor activity. This study was conducted to evaluate the antitumor activity of WRH-2412 in HCC induced in rats through affecting the TGF-ß/ß-catenin/α-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat's survival rate and by assessment of serum α-fetoprotein. Protein expression of TGF-ß, ß-catenin, E-cadherin, fascin and gene expression of SMAD4 and α-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats' survival rate and decreasing serum α-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-ß, ß-catenin, SMAD4, fascin and α-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression.

Diclofenac and Meloxicam Exhibited Anti-Virulence Activities Targeting Staphyloxanthin Production in Methicillin-Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a worldwide leading versatile pathogen that causes a wide range of serious infections. The emergence of antimicrobial resistance against S. aureus resulted in an urgent need to develop new antimicrobials in the new era. The methicillin-resistant S. aureus (MRSA) prevalence in hospital and community settings necessitates the discovery of novel anti-pathogenic agents. Staphyloxanthin (STX) is a key virulence factor for the survival of MRSA against host innate immunity. The current work aimed to demonstrate the anti-virulence properties of meloxicam (MXM) as compared to diclofenac (DC), which was previously reported to mitigate the virulence of multidrug-resistant Staphylococcus aureus and test their activities in STX production. A total of 80 S. aureus clinical isolates were included, wherein a qualitative and quantitative assessment of STX inhibition by diclofenac and meloxicam was performed. The quantitative gene expression of STX biosynthetic genes (crtM, crtN and sigB) and hla (coded for α-hemolysin) as a virulence gene with and without DC and MXM was conducted, followed by molecular docking analysis for further confirmation. DC and MXM potently inhibited the synthesis of STX at 47 and 59 µg/mL to reach 79.3-98% and 80.6-96.7% inhibition, respectively. Treated cells also revealed a significant downregulation of virulence genes responsible for STX synthesis, such as crtM, crtN and global transcriptional regulator sigB along with the hla gene. Furthermore, computational studies unveiled strong interactions between the CrtM binding site and DC/MXM. In conclusion, this study highlights the potential role and repurposing of DC and MXM as adjuvants to conventional antimicrobials and as an anti-virulent to combat MRSA infections.

Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFRWT and EGFRT790M inhibitors.

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.

A phenylpropanoid dimer from the leaves of Piper betle.

Phytochemical analyses of the chloroform extract of Piper betle L. var. Sanchi, Piperaceae, leaves led to the isolation of a new phenylpropanoid analogue for the first time: hydroxychavicol dimer, 2-(γ'-hydroxychavicol)-hydroxychavicol (S1), on the basis of spectroscopic data 1 D (1H and 13C) and 2 D (1H-1H COSY and HMBC) NMR, as well as ESI-MS, FT-IR, HR-ESI-MS and LC-ESI-MS. Compound S1 exhibited excellent antioxidant DPPH radical scavenging activity with IC50 values of 9.07 µg/mL, compared to ascorbic acid as a standard antioxidant drug with IC50 value of 3.41 µg/mL. Evaluation of cytotoxic activity against two human colon cancer cell lines (HT 29 and COLO-205) showed significant effect with GI50 values of 73.81 and 64.02 µmol/L, compared to Doxorubicin® as a standard cytotoxic drug with GI50 value of <10 µmol/L.

Influence of solvent selection and extraction methods on the determination of polyphenols, antioxidant, lipoxygenase and tyrosinase inhibition activities of Opuntia ficus-indica fruits peel and pulp collected from the Kingdom of Saudi Arabia (KSA).

The effect of extracting solvents used by two methods on the TPC, TFC, antioxidant as well as lipoxygenase, and tyrosinase inhibition activities of O. ficus-indica fruit (peel and pulp) were studied. The results manifest that extracts with solvent polarities showed different levels of polyphenols contents and antioxidant activities. The extracts acquired by the Soxhlet method were the most fascinating. Interestingly, peel extracts contain more polyphenols than pulp and showed activities. Lipoxygenase and tyrosinase inhibitory activity of the fruit peel and pulp extracts was reported for the first time. The promising results obtained prompted to the formulation of a stable phytocosmetic emulsion system loaded with 1% pre-concentrated peel extract, aiming to revive facial skin properties. The efficacy of the formulations was determined through SPF and UVA protection factors. To the in vitro safety assessment CAM-TBS, HET-CAM, and red blood cell tests were achieved. Importantly, the formulation did not induce any toxicity.